Cell penetrating peptides (CPPs) actively transport into mammalian cells across the plasma membrane barrier. CPPs are commonly derived from proteins such as the HIV-1 transcriptional activator (TAT) (Torchilin et al., 2001 Proc. Natl. Acad. Sci. 98: 8786-8791), the Antennapedia homeodomain (Antp) (Zhang et al., 2005 Biochemistry 44: 10110-10118), and the murine vascular endothelial cadherin (pVEC) (Nan et al., 2011 J. Pept. Sci. 17: 812-817). The lengths of CPPs typically range from 30-50 amino acids and such lengths can lead to preparative challenges since solid phase peptide synthesis (SPPS) methods are (commonly) utilized for their preparation (Suh et al., 2001 Comprehen. Biomat. 4: 219-245; Suh et al., 2013 Polymer Adhesion, Friction and Lubrication, 283-317 (Wiley)).
Although these CPPs have been proven to be potentially suitable for the delivery of peptides, proteins, oligonucleotides, nano-particles and any bioactive molecule into cells, they all suffer from limitations, such as their effectiveness being restricted to a subset of cargo molecules. Other peptides are relatively inefficient in the delivery of cargo molecules or have at least some specificity for delivery to various tissues (Mueller et al., Bioconjugate Chem., 2008, 19 (12), pp 2363-2374; El-Andaloussi et al., Biochem J. 2007 Oct. 15; 407(Pt 2): 285-292).
Thus, there is a need in the art to develop additional, superior CPPs. The present invention satisfies this unmet need.